Lifitegrast Ophthalmic Solution Research Articles

Effects and Safety of 5% Lifitegrast Ophthalmic Solution in Patients With Dry Eye Disease Associated With Ocular Graft-Versus-Host Disease.

Introduction Graft-versus-host disease (GVHD) is a common sequela of hematopoietic stem cell transplant (HSCT). While HSCT is often curative for certain hematologic malignancies, acute and chronic GVHD remains an important cause of morbidity and mortality in post-transplant patients. Ocular involvement is one manifestation of chronic GVHD that can present similarly to chronic dry eye with tear film abnormalities, aqueous deficiency, and corneal epithelial defects through melting and perforation. Current management includes frequent use of artificial tears and oral or topical glucocorticoids as tolerated. There is a need for long-term, steroid-sparing therapeutics in the management of ocular GVHD (oGVHD). Lifitegrast is approved for the treatment of chronic dry eye and may have therapeutic potential in the treatment of oGVHD. The aim of this study was to investigate the efficacy and safety of topical lifitegrast in the management of oGVHD. Methodology A prospective randomized clinical trial (NCT04792580) was performed on 32 enrolled patients with diagnosed oGVHD. Subjects underwent a two-week washout period consisting of preservative-free artificial tears dosed twice a day, after which they were randomized to the treatment arm (5% lifitegrast ophthalmic solution) or placebo arm (vehicle solution) for four weeks. Endpoints included Symptom Assessment iN Dry Eye (SANDE) score, unanesthetized Schirmer score, Ocular Surface Disease Index questionnaire score, fluorescein staining, tear film breakup time, meibum quantity, and turbidity. Safety endpoints included intraocular pressure, visual acuity, and rate of treatment-related adverse effects. Statistical analysis was done with a t-test or Wilcoxon rank-sum test. Results The primary and secondary efficacy endpoints were met, with statistically significant reductions in mean SANDEand unanesthetized Schirmer score observed at four weeks post-randomization. No serious adverse events related to the use of either lifitegrast or vehicle were observed, and no worsening of visual acuity or intraocular pressure occurred in the intention-to-treat analysis. However, further inference was limited due to insufficient statistical power owing to significant washout and a 50% dropout rate from the all-enrolled analysis set. The most common causes of study dropout were worsening of unrelated medical conditions (not GVHD) and improvement of SANDE score or Schirmer score outside of the inclusion criteria range during the washout period. Conclusions Lifitegrast may be a useful steroid-sparing agent in the long-term management of oGVHD. This study provides further support for the clinical evidence of lifitegrast in the management of dry eye signs and symptoms, although further sufficiently powered clinical trials are warranted to better understand its efficacy in the oGVHD population. Personalized treatment options targeting distinct manifestations of oGVHD in the cornea, tear film, lid margin, and conjunctiva are needed in the effective management of this multifaceted and complex disease.

A specific chiral HPLC method for lifitegrast and determination of enantiomeric impurity in drug substance, ophthalmic product and stressed samples

Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist used to treat the indications and symptoms associated with dry eye disease (DED), one of the most common ocular surface diseases. Lifitegrast has a chiral center, and the S-enantiomer (S-Lif) is responsible for the therapeutic effects, while the R-enantiomer (R-Lif) lacks efficacy in the treatment of DED. Lifitegrast ophthalmic solution containing 5% lifitegrast was approved by the United States Food and Drug Administration (FDA) in July 2016 for the treatment of DED in patients 17 years of age and older. The objective of this study was to develop a chiral HPLC method for the determination of the enantiomeric impurity of lifitegrast in the drug substance and in the ophthalmic product. In addition, we aimed to investigate the effect of stress and stability conditions on the enantiomeric purity of lifitegrast in both drug substance and ophthalmic solution. During the method development studies, four known lifitegrast impurities (Lif. Imp. A-D) and stressed lifitegrast samples were injected to ensure the specificity of the developed method. The enantiomers of lifitegrast are well separated with a resolution of higher than 4.0. They are also well separated from the peaks of the diluent, impurities, and the placebo used to prepare the ophthalmic solution without interference in 20 min. Chiral separation was achieved using a Chiralpak AD-H column (250 × 4.6 mm, 5.0 μm) at 40 °C with a mobile phase consisting of a mixture of n-hexane, 2-propanol, and formic acid (500:500:2, v/v/v) at a flow rate of 1.0 mL/min and a detection wavelength of 260 nm. Methanol was used as the diluent, and the drug substance solution was found to be stable for 48 h at 15 °C. The optimized chiral HPLC method for lifitegrast was validated according to ICH Q2, and the calibration curves showed excellent linearity for R-Lif (0.0369 – 1.816 µg/mL). This is the first stability-indicating, specific / selective, sensitive, linear, precise, accurate, and robust chiral HPLC method for the determination of R-Lif in S-Lif. The amount of enantiomeric impurity R-Lif in S-Lif increased under all stress and photostability test conditions without exceeding the acceptable impurity limit, with the most significant increase observed at elevated temperatures (105 °C) for both the drug substance in powder form and the ophthalmic drug solution.

Real-world treatment patterns of OTX-101 ophthalmic solution, cyclosporine ophthalmic emulsion, and lifitegrast ophthalmic solution in patients with dry eye disease: a retrospective analysis

BackgroundDry eye disease (DED) is a disorder characterized by loss of tear film homeostasis that causes ocular surface inflammation and damage. The incidence of DED increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED. This analysis compared treatment patterns in patients with DED receiving OTX-101, CsA, or LFT.MethodsThis real-world, retrospective, longitudinal cohort study utilized Symphony Health Integrated Dataverse claims from July 2019 to June 2021. The dataset included all patients with OTX-101 claims and patients with CsA or LFT claims randomly selected 2:1 to OTX-101. Patients were sorted into 3 cohorts based on index treatment. Index date was that of first treatment claim, and follow-up period was from index date to end of clinical activity or data availability. Time to treatment discontinuation (TTD), probability of discontinuation, and treatment persistence were assessed for OTX-101 vs. CsA, then OTX-101 vs. LFT. Subgroup analysis was performed based on age and prior DED treatment. Kaplan-Meier analysis and log-rank test were used to examine TTD. A logistic model evaluated association between index treatment and discontinuation. Unadjusted and adjusted odds ratios, 95% confidence intervals, and P-values were reported, with statistically significant associations based on P-values < 0.05.ResultsOverall, 7102 patients (OTX-101 n = 1846; CsA n = 2248; LFT n = 3008) were eligible. Median TTD was 354 days for patients receiving OTX-101 vs. 241 days for CsA and 269 days for LFT. Log-rank test indicated TTD was significantly longer for patients on OTX-101 vs. CsA (P = 0.033). Patients on CsA were 35% more likely to discontinue treatment than patients on OTX-101; OTX-101 and LFT groups had similar discontinuation rates. After 360 days, 49.8% of patients receiving OTX-101 remained on treatment vs. 39.4% of patients on CsA (P = 0.036) and 44.0% of patients on LFT (P = 0.854).ConclusionsPatients receiving OTX-101 remained on treatment significantly longer and were significantly less likely to discontinue treatment than patients on CsA. Older patients remained on OTX-101 significantly longer than CsA. These findings highlight treatment pattern differences in patients with DED receiving these anti-inflammatory agents.

PCR136 A Retrospective Analysis of Real-World Treatment Patterns in Patients over Age 64 with Dry Eye Disease Receiving OTX-101 Ophthalmic Solution 0.09%, Cyclosporine Ophthalmic Emulsion 0.05%, or Lifitegrast Ophthalmic Solution 5%

Dry eye disease (DED) causes chronic ocular surface inflammation and damage. DED prevalence increases with age. Cyclosporine ophthalmic solution 0.09% (CEQUA®; OTX-101), cyclosporine ophthalmic emulsion 0.05% (Restasis®; CsA), and lifitegrast ophthalmic solution 5% (Xiidra®; LFT) are anti-inflammatory agents indicated for DED treatment. We compared treatment patterns in patients >64 years with DED receiving OTX-101, CsA, or LFT.

Dry Eye Disease: Focus on Prescription Therapy

Objective To review the pharmacotherapy of prescription drugs approved for treatment of chronic dry eye disease (DED). A brief background on DED management and the pharmacist's role for care is included. Data Sources Articles indexed in PubMed (National Library of Medicine), Iowa Drug Information Service, Cochrane Reviews and Trials, and Google Scholar in the past 10 years using the key words "dry eye," "dry eye and treatment," "cyclosporine," "lifitegrast," and "varenicline." Current guidelines and manufacturers' prescribing information were reviewed. Primary sources were used to locate additional resources. Study Selection/Data Extraction Sixty-five publications were reviewed, and criteria supporting the objectives identified useful resources. Data Synthesis Selected literature included practice guidelines, review articles, research articles, product prescribing information, and drug information databases. Conclusion Patient education, eliminating causative factors, improving the daily environment for eye health, and using ocular lubricants are the first steps in DED management. A therapeutic mainstay is ocular lubricants; preservative-free formulations are recommended for chronic or repeated daily use. The Food and Drug Administration approved prescription medications for chronic use for DED, cyclosporine ophthalmic emulsion and solution, lifitegrast ophthalmic solution, and varenicline nasal spray, all improve signs and symptoms but do not cure DED. The ophthalmic products all cause ocular discomfort upon instillation. As a nasal spray, varenicline does not cause ocular discomfort, but it can cause sneezing, cough, and throat and nose irritation in some patients. Pharmacists have an opportunity to provide patient education regarding lifestyle modifications to mitigate DED and provide counseling on available products. Emerging therapies may provide advances in DED treatment.

A Validated Method Developed for Estimation of Lifitegrast in Bulk and Pharmaceutical Dosage Form by UV-Spectrophotometer and RP-HPLC

Lifitegrast is an LFA-1 antagonist, tetrahydroisoquinoline derivative, formulated as sterile eyedrops. Lifitegrast ophthalmic solution 5.0% was the first medication approved by the US FDA for treatment of the signs and symptoms of DED. We developed and validated two novel, economic, specific, and sensitive UV spectrophotometric and RP-HPLC methods for estimation of lifitegrast in bulk and dosage form. The linearity was found in the concentration range of 05-30 μg/mL in UV method (R²=0.9995) and 2-12 μg/mL in HPLC method (R²=0.999) with good correlation coefficient. The LOD and LOQ were found to be 0.77 μg/mL and 2.33 μg/mL, respectively by UV method. RP-HPLC method was developed at SunFire C 18 column (250 × 4.6 mm i.d., 5μm) using methanol, acetonitrile, and water as a mobile phase in the ratio of 20:60:20 (v/v) (pH = 2.27 adjusted with orthophosphoric acid). The LOD and LOQ were found to be 0.50 μg/mL and 1.52 μg/mL respectively by HPLC method. These developed methods were validated according to ICH (Q2 (R1)) guidelines with the following validation parameters i.e., specificity, linearity, accuracy, precision, LOD, LOQ, robustness, and ruggedness. The results of the study proved the applicability of the method in routine analysis of lifitegrast.

Efficacy of Lifitegrast Ophthalmic Solution, 5.0%, in Patients With Moderate to Severe Dry Eye Disease

An investigation of the treatment effect of lifitegrast ophthalmic solution, 5.0%, in different subgroups by severity of dry eye disease (DED) seems warranted. To explore the heterogeneity across different subgroups of DED and identify which participants were most likely to achieve clinically meaningful benefit with lifitegrast treatment. This post hoc responder analysis was performed using the data from the phase 3 OPUS-2 and OPUS-3 studies, which were 12-week, prospective, double-masked, multicenter, placebo-controlled, randomized, parallel-arm clinical trials that previously demonstrated the efficacy of lifitegrast in DED. Pooled data were stratified into 4 subgroups based on severity of inferior corneal staining score (ICSS; ≤1.5 vs >1.5) and eye dryness score (EDS; <60 or ≥60) at baseline. Data were collected from December 7, 2012, to October 5, 2015, and post hoc analysis was performed from April 14, 2020, to July 30, 2021. Lifitegrast or placebo twice daily for 84 days. Proportion of participants with (1) a clinically meaningful improvement in signs (ICSS or total corneal staining score [TCSS]) and symptoms (EDS or global visual analog scale [VAS]) and (2) a composite response for a given sign and symptom end point pair at day 84 were measured. Clinically meaningful improvement was defined as at least 30% improvement in symptoms (EDS or global VAS) and either at least a 1-point improvement in ICSS or at least a 3-point improvement in TCSS. For the composite responder analysis, the end point pairs were defined as at least a 30% reduction in EDS and at least a 1-point improvement in ICSS; at least a 30% reduction in EDS and at least a 3-point improvement in TCSS; at least a 30% improvement in global VAS and at least a 1-point improvement in ICSS; and at least a 30% improvement in global VAS and at least a 3-point improvement in TCSS. In total, 1429 participants (716 in the placebo group and 713 in the lifitegrast group) were analyzed (1087 women [76.1%]; mean [SD] age, 58.7 [14.3] years). For the overall pooled population, responder and composite responder rates favored lifitegrast vs placebo (odds ratio range, 1.29 [95% CI, 1.05-1.59] to 2.10 [95% CI, 1.68-2.61]; P ≤ .02). In the composite analysis, the subgroup with ICSS of greater than 1.5 and EDS of at least 60 at baseline (ie, moderate to severe DED) demonstrated a 1.70- to 2.11-fold higher odds of achieving clinically meaningful improvement with lifitegrast across all sign and symptom end point pairs (P ≤ .001). These post hoc findings suggest that lifitegrast ophthalmic solution, 5.0%, treatment may be associated with a response in participants with moderate to severe signs and symptoms of DED. ClinicalTrials.gov Identifier: NCT02284516.

A Post-Acute Ocular Tolerability Comparison of Topical Reproxalap 0.25% and Lifitegrast 5% in Patients with Dry Eye Disease.

PurposeTo assess the subjective eye drop experience of patients with dry eye disease (DED) over approximately 1 hour after a single dose of two formulations of reproxalap versus lifitegrast.MethodsTwo formulations of topical ocular reproxalap 0.25% were evaluated versus lifitegrast ophthalmic solution 5% in patients with DED in a single-center, double-masked, active-comparator, single-dose crossover clinical trial. Nineteen patients had test article topically administered to both eyes. Treatments were administered 2 to 4 days apart. Comfort assessments, including ocular discomfort, blurry vision, and dysgeusia assessments; ocular descriptive assessments; quality of life assessments; and overall experience questions were completed after each treatment over one hour, beginning at 90 seconds.ResultsBoth reproxalap formulations scored better in ocular discomfort score (ODS), blurry vision, and dysgeusia assessments than lifitegrast at each timepoint and cumulatively over all time points after instillation. There were lower rates of negative responses for both reproxalap formulations compared to lifitegrast across ocular discomfort, blurry vision, and dysgeusia assessments, and the durations of negative responses were shorter with reproxalap than with lifitegrast. The reproxalap groups experienced fewer quality of life impacts. No significant safety findings were observed following reproxalap or lifitegrast administration.ConclusionThe reproxalap eye drop experience over 1 hour after instillation was superior to that of lifitegrast. There were no statistically significant differences between reproxalap groups for ODS, blurry vision, or dysgeusia. The improved performance of reproxalap with regard to the most commonly reported side effects of lifitegrast (ie, ocular discomfort, blurry vision, and dysgeusia) may result in greater patient adherence and lower discontinuation rates.

Meibomian gland dysfunction is suppressed via selective inhibition of immune responses by topical LFA-1/ICAM antagonism with lifitegrast in the allergic eye disease (AED) model

PurposeThe etiology of meibomian gland dysfunction (MGD) is incompletely understood, despite being a common ophthalmic condition and an area of unmet medical need. It is characterized by an insufficiency in glandular provision of specialized lipids (meibum) to the tear film and is a major cause of dry eye. Work in the allergic eye disease (AED) mouse model has revealed an immunopathogenic role in MGD causation, now raising interest in the applicability of immunomodulatory therapies. As such, we herein ask whether inhibition of lymphocyte function associated antigen (LFA)-1/intracellular adhesion molecules (ICAM)-1 signaling via topical lifitegrast administration has a therapeutic effect on MGD in AED mice. MethodsMice were induced with AED by i.p. injection of ovalbumin (OVA) mixed with alum and pertussis toxin, followed 2 weeks later by once daily topical OVA challenges for 7 days. Mice were treated topically with 5% lifitegrast ophthalmic solution or vehicle (PBS) 30 min prior to challenge. We developed a clinical ranking method to assess MGD severity, and also scored clinical allergy. Conjunctivae and draining lymph nodes were collected for flow cytometry. ResultsTopical lifitegrast significantly inhibited clinical MGD severity, which was associated with diminished pathogenic TH17 cell and neutrophil numbers in the conjunctiva. No significant change in conjunctival TH2 cells or eosinophils, and only marginal differences in ocular allergy were observed. ConclusionsIn AED mice, lifitegrast inhibited MGD severity marked by a reduction in select immune populations in the conjunctiva. Our findings warrant future examination of lifitegrast in the treatment of patients with forms of MGD.

Real-World Experience with Lifitegrast Ophthalmic Solution (Xiidra®) in the US and Canada: Retrospective Study of Patient Characteristics, Treatment Patterns, and Clinical Effectiveness in 600 Patients with Dry Eye Disease

PurposeThis study evaluated real-world treatment of dry eye disease (DED) with lifitegrast.Patients and MethodsOphthalmologists and optometrists treating patients with DED were invited to participate through a healthcare provider (HCP)-based panel. HCPs completed a provider survey and contributed data toward a chart review for up to five qualifying patients with DED who initiated lifitegrast ophthalmic solution (index date) between 01/01/2017 (US) or 01/01/2018 (Canada) and 06/30/2019. Patient demographics, treatments, clinical characteristics, and outcomes (ie, severity, signs, symptoms) were collected for the 6-month pre-index period and up to 12-months post-index.ResultsFor this study, 517 HCPs contributed 600 patient charts. Among 554 and 281 patients with follow-up at 6 and 12-months post-index, 512 (92.4%) and 238 (84.7%) patients had ongoing lifitegrast treatment, respectively. Other DED-related treatments were less frequently used post-index with lifitegrast vs pre-index: over-the-counter artificial tear use (45.2% vs 75.5%), topical corticosteroids (3.8% vs 18.8%), any cyclosporine (3.0% vs 20.5%). At 3-months (n=571) and 12-months (n=320) post-index vs pre-index, fewer patients had eye dryness (47 [8.2%] and 16 [5.0%] vs 525 [87.5%]), blurred vision (28 [4.9%] and 11 [3.4%] vs 346 [57.7%]), ocular burning/stinging (25 [4.4%] and 8 [2.5%] vs 336 [56.0%]), depression (8 [1.4%] and 9 [2.8%] vs 55 [9.2%]), fatigue (4 [0.7%] and 1 [0.3%] vs 82 [13.7%]), and headache (1 [0.2%] and 0 vs 19 [3.2%]). At 3 and 12-months post-index vs pre-index, average corneal staining score was numerically lower (2.7 and 2.0 vs 6.5), and average Schirmer score (10.6 and 10 vs 6.3) and tear film break-up time (7.3 and 8.0 vs 4.8) higher.ConclusionThe majority of patients had ongoing lifitegrast treatment 6-months post-index with reduction in overall treatment burden. Improvement in DED signs and symptoms, including QoL impacts, was evident at 3 months and up to 12 months after lifitegrast initiation.

The Effect of Lifitegrast on Refractive Accuracy and Symptoms in Dry Eye Patients Undergoing Cataract Surgery.

PurposeTo determine the effect of lifitegrast ophthalmic solution 5% on improving the tear film, biometry/keratometry, and refractive accuracy for dry eye patients scheduled for cataract surgery.Patients and MethodsMulticenter, prospective, open-label study of 100 eyes of 100 patients undergoing cataract surgery who had a confirmed diagnosis of dry eye. Patients underwent biometry at baseline and again after a 28-day course of lifitegrast 5% BID. Primary outcome was an improvement in the accuracy of preoperative anterior corneal power measurements at predicting postoperative spherical equivalent (SE) pre- and post-lifitegrast treatment. Secondary outcomes included changes in dry eye symptoms and corneal staining.ResultsThe accuracy of the biometry readings for the achieved refractive SE: within 0.25 D in 47% and 50% of eyes before and after the initial lifitegrast treatment, respectively; within 0.5 D in 71% and 79% of eyes before and after the initial lifitegrast treatment; and within 0.75 D in 81% and 91% of eyes before and after the initial lifitegrast treatment (p < 0.04).ConclusionLifitegrast 5% significantly improved preoperative corneal surface measurement accuracy in patients with confirmed dry eye who were scheduled for cataract surgery.

Punctal eversion with silicone plug resulting in ocular surface trauma

A woman in her 70s with a history of chronic mixed mechanism ocular surface disease presented with an epithelial defect in her left eye. She was status post lower punctal...

A 6-Week, Prospective, Randomized, Single-Masked Study of Lifitegrast Ophthalmic Solution 5% Versus Thermal Pulsation Procedure for Treatment of Inflammatory Meibomian Gland Dysfunction

Meibomian gland dysfunction (MGD) is present in most cases of dry eye disease. MGD involves both inflammatory and obstructive etiologies. We compared efficacy and safety of treatment to reduce inflammation (lifitegrast) versus obstruction [thermal pulsation procedure (TPP)] in patients with inflammatory MGD over 42 days. This was a single-center, 6-week, prospective, randomized, single-masked study of adults with inflammatory MGD, defined as having all of the following: burning, stinging, dryness; thickened secretions or occlusion of glands; eyelid redness; and elevated matrix metalloproteinase-9. Patients received lifitegrast ophthalmic solution 5% twice daily for 42 days or one TPP treatment at day 0. Seven symptoms and 8 objective measures of dry eye disease were assessed. Overall, 40 of 50 randomized patients (80%) were women with mean (SD) age 65.8 (8.9) years. Lifitegrast-treated (n = 25) versus TPP-treated (n = 25) patients had greater improvement from baseline to day 42 in eye dryness [mean (SD) change from baseline: -1.05 (0.79), lifitegrast; -0.48 (0.96), TPP; P = 0.0340], corneal staining [-0.55 (0.80), lifitegrast; 0.12 (1.09), TPP; P = 0.0230], and eyelid redness [-0.77 (0.43), lifitegrast; -0.38 (0.58), TPP; P = 0.0115]; trend favored lifitegrast for best corrected visual acuity and gland patency. Unexpectedly, TPP treatment did not improve lipid layer thickness or gland patency compared with lifitegrast. No adverse events were reported. Although MGD is often considered a disease of gland obstruction, these findings demonstrate antiinflammatory treatment with lifitegrast significantly improved patient symptoms and signs compared with treatment for obstruction (TPP). Lifitegrast should be included in treatment for inflammatory MGD.

Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease

Ocular chronic graft-versus-host disease (oGVHD) is a relatively common complication that occurs following allogeneic hematopoietic cell transplantation. Keratoconjunctivitis sicca (KCS) is the most common manifestation of oGVHD. Lifitegrast is a lymphocyte function-associated antigen-1 antagonist approved to reduce inflammation and symptoms in patients with dry eye disease. We evaluated the efficacy and safety of lifitegrast (5% ophthalmic solution) in patients with ocular GVHD in a single-institution retrospective cohort study of eighteen allogeneic transplant recipients who received topical lifitegrast for oGVHD treatment. The outcome of interest was improvement in oGVHD severity score by National Institutes of Health (NIH) criteria. Lifitegrast was well-tolerated and no serious adverse events were observed. Lifitegrast significantly improved NIH severity scores in 8 (44%) patients. The findings of this study suggest lifitegrast is safe, well-tolerated and is an effective option for oGVHD manifesting as KCS. Prospective evaluation is warranted to confirm efficacy of lifitegrast in this population.HighlightsIn this single-institution retrospective cohort study of eighteen patients who received allogeneic transplant between 2013 and 2018, and received topical lifitegrast for treatment of ocular GVHD, the results demonstrate that lifitegrast eye drops were well-tolerated and led to improvement in symptoms of KCS in 8 (44%) patients.Lifitegrast has the potential to fulfill an unmet need in allogeneic transplant patients with ocular GVHD. Further prospective study is warranted for confirmation.

Real-World Treatment Patterns Of Cyclosporine Ophthalmic Emulsion And Lifitegrast Ophthalmic Solution Among Patients With Dry Eye.

PurposeTo assess adherence, non-persistence, discontinuation, and switching of topical cyclosporine ophthalmic emulsion 0.05% (CYC) and lifitegrast ophthalmic solution 5% (LIF) use in the real world among patients with dry eye disease (DED).DesignRetrospective insurance claims study.MethodsAdult patients with DED and ≥1 prescription claim for CYC or LIF (first claim = index date) in the IBM® MarketScan® databases from July 2016 to February 2018 were identified. Eligible patients had continuous medical and pharmacy benefits in the 12 months pre- and post-index periods, and no prior use of the index medication. The proportion of days covered (PDC), adherence, non-persistence, discontinuation, and switching were examined over the 12-month post-index period.ResultsThis study included 6537 CYC and 3235 LIF patients. The adherence rate was 5.9% for CYC and 9.7% for LIF; the median PDC was 0.3 for both cohorts. Overall, 70.8% of CYC and 64.4% of LIF patients discontinued treatment with median days to discontinuation of 89 and 29, respectively. Non-persistence was 7.1% for CYC and 6.8% for LIF (median days to discontinuation: 89 and 105). In addition, 5.0% switched from CYC to LIF, and 9.6% switched from LIF to CYC over the post-index period.ConclusionOver 60% of DED patients discontinued treatment within 12 months of initiation; the median time to discontinuation was 3 months for CYC and 1 month for LIF. Although this analysis did not capture the reasons why patients discontinued treatment, the results demonstrate there likely exists a significant unmet need amongst DED patients.

Six months' treatment with lifitegrast in patients with moderate-to-severe symptomatic dry eye: a retrospective chart review.

PurposeTo evaluate 6-month treatment benefits with lifitegrast ophthalmic solution 5% in symptomatic dry eye patients.SettingRetrospective chart analysis.MethodA retrospective chart review was conducted in 168 patients (111 females and 57 males) who presented with symptoms of chronic dry eye disease and were treated with lifitegrast 5% ophthalmic solution for 6 months. Collected symptom data included improvement of eye dryness, tearing, eye pain, fluctuation in vision, foreign body sensation, itching, grittiness, burning and contact lens intolerance if applicable. Collected clinical signs included changes in superficial punctate keratitis, corneal fluorescein staining, conjunctival hyperemia and presence of tear debris.ResultsTreatment with lifitegrast ophthalmic solution 5% twice daily for 6 months significantly improved majority of dry eye symptoms reported by patients. Improvements were also observed in corneal and conjunctival staining and tear debris for most of the patients reviewed.ConclusionTreatment with lifitegrast twice a day for 6 months improved both signs and symptoms of chronic dry eye.

Longitudinal changes in dry eye symptoms and signs following lifitegrast therapy and relationship to tear osmolarity.

BackgroundThis study measured longitudinal changes in dry eye disease (DED) symptoms and signs following lifitegrast therapy and assessed their relationship to tear osmolarity to test the hypothesis that a decline in tear osmolarity is a reliable leading indicator of subsequent improvement in DED symptoms and signs after initiating lifitegrast treatment.MethodsThis phase IV, prospective, single-arm, open-label, 12-week study enrolled subjects aged ≥18 years with eye dryness score ≥40 (0–100 VAS) and tear osmolarity ≥308 mOsm/L. Subjects were prescribed lifitegrast ophthalmic solution 5%, twice daily in each eye. DED symptoms were assessed via VAS at baseline and 2, 6, and 12 weeks. Signs included tear osmolarity, meibomian gland dysfunction, tear breakup time, and fluorescein corneal staining. In post-hoc analysis, subjects with ≥5 mOsm/L decrease in osmolarity over 12 weeks were Responders.ResultsOf 26 subjects in the intent-to-treat population, 23 were female; mean age was 67.4 years. Baseline mean±SD eye dryness was 68.7±16.5 and tear osmolarity was 317.8±8.5 mOsm/L. All seven symptoms (dryness, burning, foreign body sensation, pain, photophobia, itching, blurred vision) declined significantly (P<0.01) from baseline to 6 and 12 weeks. Signs did not change significantly. For 13 Responders, tear osmolarity decreased from baseline to 12 weeks (319.2±8.5 to 300.6±12.3 mOsm/L, P<0.001) and corneal staining trended toward improvement (1.1±0.9 to 0.6±0.7, P=0.136). Among Nonresponders, osmolarity increased from 316.4+8.7 to 329.6+13.9 (P<0.01) and corneal staining showed no change (1.3±0.8 to 1.0±0.7 at 12 weeks, P=0.293).ConclusionsLifitegrast reduced DED symptoms among subjects with moderate-to-severe disease (severity defined by VAS for eye dryness). Potential reasons that may underlie the dichotomous effect of drug treatment on tear osmolarity are discussed.

Lifitegrast Ophthalmic Solution 5.0% for Treatment of Dry Eye Disease: Overview of Clinical Trial Program.

Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to inhibit DED-associated ocular inflammation. Four clinical trials have shown that lifitegrast is well tolerated and effective in improving symptoms and signs of DED over 12 weeks. A fifth trial showed long-term safety over 1 year. Lifitegrast has been in clinical use for more than one year in the United States and was recently approved in Canada (in December 2017). In this review, we discuss lifitegrast's novel mechanism of action and provide an overview of its clinical trial program.

Erratum: Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial [Corrigendum

[This corrects the article on p. 263 in vol. 12, PMID: 29440868.].

Ocular comfort assessment of lifitegrast ophthalmic solution 5.0% in OPUS-3, a Phase III randomized controlled trial.

PurposeTo evaluate ocular comfort of lifitegrast ophthalmic solution 5.0% among patients with dry eye disease (DED) in the OPUS-3 trial.MethodsOPUS-3 was a multicenter, randomized, double-masked, placebo-controlled study. Adults with DED and recent artificial tear use were randomized 1:1 (lifitegrast:placebo) to ophthalmic drops twice daily for 84 days. On days 0 (baseline), 14, 42, and 84, drop comfort score (scale, 0–10; 0 = very comfortable, 10 = very uncomfortable) was measured at 0, 1, 2, and 3 minutes postinstillation. If the score was >3 at 3 minutes, assessment was repeated at 5, 10, and 15 minutes until score ≤3. Ocular treatment-emergent adverse events (TEAEs) were assessed.ResultsOverall, 711 participants were randomized (n=357 received lifitegrast; n=354 received placebo). Drop comfort scores for lifitegrast-treated participants improved within 3 minutes of instillation (mean scores on day 84 for both study and fellow eyes: instillation: lifitegrast, 3.4, placebo, 1.0; 3 minutes: lifitegrast, 1.5, placebo, 0.7). The majority (64%–66%) of participants had scores <3 within 3 minutes postinstillation on days 14, 42, and 84. In participants with scores >3 at 3 minutes, the mean score in the lifitegrast group was similar to or better than that in the placebo group at 5, 10, or 15 minutes postinstillation. Lifitegrast appeared to be well tolerated, with ocular TEAEs rarely leading to discontinuation.ConclusionIn OPUS-3, lifitegrast appeared to be well tolerated and drop comfort scores approached placebo levels by 3 minutes postinstillation.